Dr. Grzegorz Popowicz
Institute of Structural Biology
Helmholtz Zentrum München
Ingolstädter Landstr. 1
My primary research activity is drug discovery with focus on protein-protein interaction and new targets scouting. Protein-protein interactome offer enormous number of Protein-Protein Interactions (PPI) that can be used as therapeutic targets using small molecules. The applicability of PPI targeting has been confirmed only recently. However, development of PPI modulators is difficult due to lack of substrates that can be used as a starting point for analogue development and usually large interfaces with dispersed binding energies. PPI usually require compounds of unique chemical properties seldom found in contemporary screening libraries. I am using structure-based computational methods to identify PPIs modulators. With a help of fragmentbased screening, NMR-based SAR evaluation and X-ray crystallography I design molecules that can serve as a chemical probe to validate PPI therapeutic proof-of-concept and be optimized into drug candidates.
Further, my research interest includes:
- Multicomponent ligand chemistry, computational synthesis design
- Integration of fragment based and multicomponent approach
- Employing transient, dynamic states of the interface to optimize ligands
- SAR by X-ray and NMR
- Structural biology of the complexes
- Assay development, target scouting
Until recently (2012) my primary research focus was investigation of therapeutic opportunities of p53-Mdm2/MdmX systems. I have published first structures of p53-MdmX complex and first structure of MdmX with small molecule inhibitor. My work was also focused around improving structural diversity of compound libraries and computational tools to aid in this task. Since 2012, I become Facility Manager coordinating Fragment- and Structure-based drug discovery activities of Institute of Structural Biology (STB) at Helmholtz Zentrum München. I am currently studying 16 potential new biomolecular targets derived from HMGU basic research. The principle of my work is to integrate structural biology data (rational molecule design, 3D screening), fragment-based drug discovery (NMR-based) and advanced medicinal chemistry with particular focus on multicomponent synthesis.
- Hennig J, Militti C, Popowicz GM, Wang I, Sonntag M, Geerlof A, Gabel F, Gebauer F, Sattler M. Nature. 2014 515:287-90.
- Baek S, Kutchukian PS, Verdine GL, Huber R, Holak TA, Lee KW, Popowicz GM. Structure of the stapled p53 peptide bound to Mdm2. J Am Chem Soc. 2012 134:103-6.
- Popowicz GM, Dömling A, Holak TA. Structure-based, rational design of Mdm2/Mdmx-p53 inhibitors gets serious. Angew Chem Int Ed Engl. 2011 50: 2680-2688.